NELL-1 Membranous Nephropathy during treatment of Rheumatoid Arthritis with Adalimumab

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Joselyn

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Reyes Bahamonde

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Introduction

Neural epidermal growth factor-like 1 protein (NELL-1) was discovered as a membranous nephropathy (MN) antigen by Dr Sethi et al. NELL-1 has been associated with malignancy, use of traditional medicine, and lipoic acid supplements. Here we report a case of a patient who developed nephrotic syndrome (NS) and NELL-1 MN after initiation of Adalimumab

Methods

57 yo woman was evaluated for nephrotic syndrome in January of 2022. Past medical history was significant for obesity (BMI 31), pulmonary embolism treated with Eliquis, and rheumatoid arthritis (RA) with +RF and +CCP Ab. History of RA was significant for symmetric arthritis with multiple flares. Initial treatment for RA was Prednisone, and Adalimumab was added in April of 2021 and was discontinued due to side effects in October of 2021, 3 months before nephrology evaluation. Later, the patient was transitioned to Methotrexate and Plaquenil. Hypoalbuminemia was found 4 months after initiation of Adalimumab (Figure 1). Physical exam revealed blood pressure 140/90mmHg, and peripheral edema. Serum creatinine was 0.98mg/dL, albumin 2mg/dL. Urinalysis revealed 3+ proteins, UACr 9,890mg/dL, UPCr 5.41 g/g. Serologic testing was negative for ANA, dsDNA, hepatitis B and C, ANCA, and complements were normal. A kidney biopsy was performed, and NELL-1 Membranous Nephropathy was diagnosed (Figure 2). After diagnosis, the age-appropriate malignancy screening was negative and the patient received 2 doses of Rituximab, 1gr separated by 2 weeks. Proteinuria improved to 0.5g/g with the resolution of NS.

Results

Conclusions

NELL-1 has been linked to malignancy and traditional medicine, but it has not been associated with Adalimumab. Our patient had a long history of RA but never developed kidney complications associated with her chronic inflammatory autoimmune disease however, the patient developed hypoalbuminemia and NS four months after the initiation of Adalimumab. This is not the first time Adalimumab has been linked with MN. In 2011, before the discovery of NELL-1 Gupta et al described a case of MN in a patient with Chron’s disease four months after the initiation of the humanized anti-Tumor Necrosis Factor α, Adalimumab. We hypothesize that the well-known antibody production against Adalimumab plays a role in NELL-1 expression in MN. Further studies are needed to investigate this potential association.

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